Novel Uses of Methadone Under the "72-Hour Rule" to Facilitate Transitions of Care and Low-Dose Buprenorphine Induction in an Outpatient Bridge Clinic.

BACKGROUND: Federal regulations restrict methadone for opioid use disorder (OUD) treatment to licensed opioid treatment programs (OTPs). However, providers in other settings can administer methadone for opioid withdrawal under the "72-hour rule" while linking to further care. Prior work has demonstrated that methadone initiation in a low-barrier bridge clinic is associated with high OTP linkage and 1-month retention rates. We describe 2 other novel applications of the 72-hour rule in which methadone withdrawal management facilitated linkage to inpatient hospitalization and outpatient buprenorphine induction. CASE PRESENTATIONS: Patient 1 was a 46-year-old woman with OUD complicated by serious injection-related infections. Severe opioid withdrawal limited her ability to tolerate emergency department wait times and receive inpatient care. We administered methadone for opioid withdrawal in an outpatient bridge clinic immediately before emergency department referral; this enabled hospital admission for intravenous antibiotics and anticoagulation. Patient 2 was a 36-year-old man with OUD desiring buprenorphine treatment. He had been unable to complete traditional buprenorphine induction without experiencing precipitated withdrawal. Thus, we recommended a low-dose buprenorphine induction overlapping with a full opioid agonist. Given the patient's preference to stop using fentanyl immediately, he received 72 hours of methadone for withdrawal treatment during the induction phase and successfully transitioned to buprenorphine without significant concomitant fentanyl use. CONCLUSION: In addition to facilitating OTP linkage, on-demand 72-hour methadone administration for opioid withdrawal can reduce barriers to acute medical care and buprenorphine treatment.

Limited English Proficiency and Sepsis Mortality by Race and Ethnicity.

Importance: Patients with limited English proficiency (LEP) face multiple barriers and are at risk for worse health outcomes compared with patients with English proficiency (EP). In sepsis, a major cause of mortality in the US, the association of LEP with health outcomes is not widely explored. Objective: To assess the association between LEP and inpatient mortality among patients with sepsis and test the hypothesis that LEP would be associated with higher mortality rates. Design, Setting, and Participants: This retrospective cohort study of hospitalized patients with sepsis included those who met the Centers for Disease Control and Prevention's sepsis criteria, received antibiotics within 24 hours, and were admitted through the emergency department. Data were collected from the electronic medical records of a large New England tertiary care center from January 1, 2016, to December 31, 2019. Data were analyzed from January 8, 2021, to March 2, 2023. Exposures: Limited English proficiency, gathered via self-reported language preference in electronic medical records. Main Outcomes and Measures: The primary outcome was inpatient mortality. The analysis used multivariable generalized estimating equation models with propensity score adjustment and analysis of covariance to analyze the association between LEP and inpatient mortality due to sepsis. Results: A total of 2709 patients met the inclusion criteria, with a mean (SD) age of 65.0 (16.2) years; 1523 (56.2%) were men and 327 (12.1%) had LEP. Nine patients (0.3%) were American Indian or Alaska Native, 101 (3.7%) were Asian, 314 (11.6%) were Black, 226 (8.3%) were Hispanic, 38 (1.4%) were Native Hawaiian or Other Pacific Islander or of other race or ethnicity, 1968 (72.6%) were White, and 6 (0.2%) were multiracial. Unadjusted mortality included 466 of 2382 patients with EP (19.6%) and 69 of 327 with LEP (21.1%). No significant difference was found in mortality odds for the LEP compared with EP groups (odds ratio [OR], 1.12 [95% CI, 0.88-1.42]). When stratified by race and ethnicity, odds of inpatient mortality for patients with LEP were significantly higher among the non-Hispanic White subgroup (OR, 1.76 [95% CI, 1.41-2.21]). This significant difference was also present in adjusted analyses (adjusted OR, 1.56 [95% CI, 1.02-2.39]). No significant differences were found in inpatient mortality between LEP and EP in the racial and ethnic minority subgroup (OR, 0.99 [95% CI, 0.63-1.58]; adjusted OR, 0.91 [95% CI, 0.56-1.48]). Conclusions and Relevance: In a large diverse academic medical center, LEP had no significant association overall with sepsis mortality. In a subgroup analysis, LEP was associated with increased mortality among individuals identifying as non-Hispanic White. This finding highlights a potential language-based inequity in sepsis care. Further studies are needed to understand drivers of this inequity, how it may manifest in other diverse health systems, and to inform equitable care models for patients with LEP.

Grayken lessons: the role of an interdisciplinary endocarditis working group in evaluating and optimizing care for a woman with opioid use disorder requiring a second tricuspid valve replacement.

BACKGROUND: Injection drug use-related endocarditis is increasingly common among hospitalized patients in the United States, and associated morbidity and mortality are rising. CASE PRESENTATION: Here we present the case of a 34-year-old woman with severe opioid use disorder and multiple episodes of infective endocarditis requiring prosthetic tricuspid valve replacement, who developed worsening dyspnea on exertion. Her echocardiogram demonstrated severe tricuspid regurgitation with a flail prosthetic valve leaflet, without concurrent endocarditis, necessitating a repeat valve replacement. Her care was overseen by our institution's Endocarditis Working Group, a multidisciplinary team that includes providers from addiction medicine, cardiology, infectious disease, cardiothoracic surgery, and neurocritical care. The team worked together to evaluate her, develop a treatment plan for her substance use disorder in tandem with her other medical conditions, and advocate for her candidacy for valve replacement. CONCLUSIONS: Multidisciplinary endocarditis teams such as these are important emerging innovations, which have demonstrated improvements in outcomes for patients with infective endocarditis and substance use disorders, and have the potential to reduce bias by promoting standard-of-care treatment.

Rethinking Home-based Outpatient Parenteral Antibiotic Therapy for Persons Who Inject Drugs: An Opportunity for Change in the Time of COVID-19.

Outpatient parenteral antibiotic therapy (OPAT) refers to the monitored provision of intravenous antibiotics for complicated infections outside of a hospital setting, typically in a rehabilitation facility, an infusion center, or the home. Home-based OPAT allows for safe completion of prolonged courses of therapy while decreasing costs to the healthcare system, minimizing the risk of hospital-related infectious exposures for patients, and permitting patients to recover in a familiar environment. Amidst the COVID-19 pandemic, during which nursing facilities have been at the center of many outbreaks of the SARS-CoV-2 virus, completion of antimicrobial therapy in the home is an even more appealing option. Persons who inject drugs (PWID) frequently present with infectious complications of their injection drug use which require long courses of parenteral therapy. However, these individuals are frequently excluded from home-based OPAT on the basis of their addiction history. This commentary describes perceived challenges to establishing home-based OPAT for PWID, discusses ways in which this is discriminatory and unsupported by available data, highlights ways in which the COVID-19 pandemic has accentuated inequities in care, and proposes a multidisciplinary approach championed by Addiction specialists to increasing implementation of OPAT for appropriate patients with substance use disorders.

Training junior doctors to lead rapid responses.

BACKGROUND: Transitions during medical training are a significant source of stress, and junior doctors (residents) primarily learn new skills through on-the-job training. As residents transition from postgraduate year (PGY) 1 to 2, they take on new responsibilities, including the management of clinically unstable patients in rapid response (RR) scenarios. APPROACH: In 2018, the internal medicine training programme at Brigham and Women's Hospital implemented a 'Transitions Retreat' to prepare PGY-1s for Year 2. In an informal survey, residents endorsed feeling underprepared to lead RRs. We designed a simulation-based curriculum to teach these skills. Participants completed a questionnaire pre-simulation and post-simulation exploring their perceived preparedness. Volunteer residents assessed performance on the simulation using skills checklists and led structured debriefing sessions. We audiotaped, transcribed and thematically analysed these sessions. EVALUATION: Forty-eight of 58 (82%) PGY-1s participated. Pre-intervention, 12.5% felt 'well-prepared' or 'very well-prepared' to lead RRs, compared with 33% post-intervention. Through qualitative analysis, we identified four key themes in our post-simulation debriefing conversations: (1) the chaos of RRs, (2) emotional reactions during RRs, (3) challenges and goals of task management and (4) value of interdisciplinary collaboration. IMPLICATIONS: Though the majority of residents indicated that the curriculum enabled their preparedness to lead RRs and allowed them to process complex emotions in a safe space, we do not know how well this experience translates to the clinical setting. Therefore, we aim to collect follow-up data 6 months into the PGY-2 to explore residents' reflections on real-life experiences as well as whether the simulation impacted their preparedness to lead real-life RRs.

Using Chart-Stimulated Recall to Identify Barriers and Facilitators to Routine HIV Testing Among Pediatric Primary Care Providers.

PURPOSE: Adolescents account for one in five new HIV infections in the U.S. Yet, only 25% of sexually active adolescents report HIV testing, and testing rates have not improved over time. In this study, the primary aim was to identify barriers and facilitators to routine HIV testing in the pediatric primary care setting. METHODS: Practices within a large pediatric network were stratified by higher and lower rates of HIV testing. Providers were purposively sampled across practices, and chart-stimulated recall was used to explore HIV testing knowledge and practices by having providers review actual adolescent well visit records. Interviews were audio-recorded and transcribed. Qualitative content analysis identified categories of barriers and facilitators to HIV testing among higher and lower performing sites. RESULTS: Of participants (n = 31), 52% were from higher performing clinics, and 48% from lower performing clinics, and mean number of years in practice was 16.9 (standard deviation 10.8). Provider-identified barriers at lower-performing sites included lack of knowledge of testing guidelines, inadequate sexual risk assessment, concerns about damaging patient/caregiver relationships, and competing priorities, whereas both high- and low-performing cites reported concerns about confidentiality. Identified facilitators at higher performing sites included availability of on-site resources (Title X funding; laboratory). CONCLUSIONS: Several distinct barriers and facilitators to routine HIV screening were identified at lower and higher performing sites. These findings can inform the development of multilevel interventions to improve HIV testing rates in pediatric primary care.

Tumor cell invasion is promoted by interstitial flow-induced matrix priming by stromal fibroblasts.

Interstitial flow emanates from tumors into the microenvironment where it promotes tumor cell invasion. Fibroblasts are key constituents of the tumor stroma that modulate the mechanical environment by matrix remodeling and contraction. Here, we explore how interstitial fluid flow affects fibroblast-tumor cell interactions. Using a 3-dimensional invasion assay and MDA-MB-435S cells cocultured with dermal fibroblasts in a collagen matrix, we showed a synergistic enhancement of tumor cell invasion by fibroblasts in the presence of interstitial flow. Interstitial flow also drove transforming growth factor (TGF)-ß1 and collagenase-dependent fibroblast migration, consistent with previously described mechanisms in which flow promotes invasion through autologous chemotaxis and increased motility. Concurrently, migrating fibroblasts enhanced tumor cell invasion by matrix priming via Rho-mediated contraction. We propose a model in which interstitial flow promotes fibroblast migration through increased TGF-ß1 activation and collagen degradation, positioning fibroblasts to locally reorganize collagen fibers via Rho-dependent contractility, in turn enhancing tumor cell invasion via mechanotactic cues. This represents a novel mechanism in which interstitial flow causes fibroblast-mediated stromal remodeling that facilitates tumor invasion.